Molecular Imaging & Spectroscopy

Wednesday 14 May 2014   10:00 - 11:00

Space 1/Power Poster Theatre & Traditional Poster Hall 
Moderators: Jerry D. Glickson Ph.D., Michal Neeman, Ph.D.

Karl F. Stupic¹, Kathryn E. Keenan¹, Edward V. Denison¹, Charles A. E. Little¹, and Stephen E. Russek^1
1National Institute of Stanards and Technology, Boulder, Colorado, United States

A new class of nanofabricated contrast agents, which operate as nano-resonators, is proposed and modeled. The agents are based on nanoscale synthetic antiferromagnets (nano-SAFs) which have resonant modes that are engineered to have large spectral densities at MRI proton frequencies. The resonance frequencies can be adjusted by tuning the layer thicknesses to give the desired resonances at all clinical field strengths. Initial nano-SAFs, with 830 nm diameter and 70 nm thicknesses, have been fabricated and imaged at 1.5 T. Strong T1 contrast was not observed indicating that smaller dimensions are required.

Yuguo Li^1,2, Kannie Chan^1,2, peter van Zijl^1,2, Bert Vogelstein³, Michael McMahon^1,2, Shibin Zhou³, and Guanshu Liu^1,2
1Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²FM Kirby center, Kennedy Krieger Institute, Baltimore, MD, United States, ³Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Non-invasive tracking of drug delivery is of great clinical interest. Herein, we explored a direct way to track liposome mediated delivery of gemcitabine, a first-line drug for treating pancreatic cancer. We show that this can be achieved using its inherent Chemical Exchange Saturation Transfer (CEST) MRI signal at 2.1 and 1.0 ppm originating from the exchangeable amino and hydroxyl protons, respectively. Unlike traditional approaches, the CEST MRI detection doesn’t require the use of extra contrast agents, and is able to directly convert the gemcitabine-loaded nanoparticle drug delivery system into a theranostic system.

Giuseppe Ferrauto¹, Enza Di Gregorio¹, Daniela Delli Castelli¹, Enzo Terreno¹, and Silvio Aime^1
1Molecular Biotechnologies & Health Sciences, Molecular Imaging Center, Torino, Italy

Three key hallmarks of the tumor development are represented by the increased vascular volume, the enhanced vascular permeability and the acidification of the extracellular/extravascular pH (pHe). CEST contrast agents appear well suitable to visualize simultaneously the three biomarkers by using the currently available 1H-MRI scanners. YbHPDO3A, a small hydrophilic, well tolerated paraCEST agent, chemical analogue of the clinically approved ProHance, provides the way to get information both on change in pHe and on change in vascular permeability. Semi-quantitative information on the vascular volume have been obtained by using Dysprosium- loaded Red Blood Cells, a new kind of CEST contrast agent.

Eric T Ahrens¹, Anthony Balducci², Brooke Helfer², Amy Wesa², Charles O'Hanlon², Claudiu Schirda³, David Bartlett⁴, and Pawel Kalinski^4
1Radiology, University of California at San Diego, La Jolla, CA, United States, ²Celsense, Inc., Pittsburgh, PA, United States, ³Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, United States

Cell therapies, such as those employing immune or stem cells, can benefit from non-invasive imaging to visualize cells following transfer into the patient. We described the first clinical use of a fluorine-19 MRI tracer agent designed for MRI cell tracking. We labeled autologous immunotherapeutic dendritic cells (DCs) with a perfluorocarbon (PFC) tracer agent ex vivo. Labeled DCs were inoculated into colorectal cancer patients. Cells were detected using a 3T scanner using 19F MRI/MRS. Clinical 19F-based cell tracking is feasible and provides unambiguous information about the cell location, with no background signal, and can be used to quantify cells in situ.

Klaus Möllenhoff¹, Jörg Felder¹, Sandro Romanzetti¹, Ali Gordji-Nejad¹, and N Jon Shah^1,2
1INM-4, Research Centre Jülich GmbH, Jülich, Germany, ²Department of Neurology, RWTH Aachen University, Aachen, Germany

Knowledge of quantitative values of CMRO2 is of great interest to follow the treatment of the diseases. In the last decades, 15O was used to quantify CMRO2 with the use of PET imaging as a gold standard. In this preliminary study we show the feasibility of in vivo 17O imaging experiments with a sufficient SNR in acceptable measurement times at 9.4T in humans.

Myriam M Chaumeil¹, Peder E.Z. Larson¹, Sarah M Woods¹, Pia Eriksson¹, Larry Cai¹, Aaron Robinson², Daniel B Vigneron¹, Sarah J Nelson¹, Russell O Pieper², Joanna J Phillips², and Sabrina M Ronen^1,2
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ²Brain Tumor Research Center, UCSF, San Francisco, CA, United States

Following injection of hyperpolarized α-ketoglutarate, we previously reported the detection of hyperpolarized 2-hydroxyglutarate formation in IDH1-mutant tumors, not in in IDH1 wild-type, using 2D ¹³C dynamic CSI at clinical field strength. Here, we show that, contrarily to 2-hydroxyglutarate, hyperpolarized glutamate formation from hyperpolarized α-ketoglutarate could be detected in IDH1 wild-type perfused cells and tumors only, not in cells or tumors harboring the IDH1 mutation. Biochemical assays were performed to assess the underlying mechanisms. Hyperpolarized glutamate could thus potentially serve as a non-invasive additional surrogate marker of IDH1 mutational status in brain tumors.

P. Stephen Patrick¹, Mikko I. Kettunen^1,2, Sui-Seng Tee¹, Tiago B. Rodrigues¹, Eva M. Serrao¹, Kerstin Timm¹, and Kevin M. Brindle^1
1CRUK Cambridge Institute and Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ²A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

Diffusion spectroscopy of hyperpolarized [¹³C]urea was used to assess urea transporter expression as a potential gene reporter in vivo. Significantly decreased apparent diffusion coefficient was measured for urea transporter expressing tumors compared to their non-expressing controls. No differences in tumor cellularity were observed. The results suggest that expression of transporter in combination with diffusion spectroscopy might be used as another approach for detecting gene reporter expression.

Changho Choi¹, Sandeep Ganji¹, Zhongxu An¹, and Akshay Madan^1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

We report regional variations in metabolite levels in healthy human brain, focusing on GABA, glutamate, glutamine, and N-acetyl-aspartyl-glutamate. A GABA-tailored PRESS sequence (TE = 92 ms) was used, at 7T, to measure the metabolites in gray matter (GM) and white matter (WM) dominant regions in the frontal and occipital brain in 9 healthy volunteers. Metabolite levels in pure GM and WM were obtained with linear regression of metabolite estimates vs. fractional GM contents. The result indicated that the concentrations of many metabolites are significantly different between frontal and occipital brain as well as between GM and WM.

Wolfgang Bogner¹, Borjan Gagoski², Aaron T Hess³, Bernhard Strasser¹, Himanshu Bhat⁴, Dylan Tisdall⁵, Andre J.W. van der Kouwe⁵, Ellen Grant², Siegfried Trattnig¹, Bruce Rosen⁵, and Ovidiu C Andronesi^5
1High-field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Vienna, Austria, ²Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, United States, ³Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford, United Kingdom,⁴Siemens Healthcare, Charlestown, United States, ⁵Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States

GABA, the major inhibitory neurotransmitters, is difficult to detect. Single-voxel MEscher-GArwood (MEGA) PRESS editing MRS is the most popular technique for non-invasive detection of GABA, but it has several limitations: MEGA editing is a subtraction technique and, therefore, prone to scanner instabilities and motion artifacts. Chemical shift displacement errors (CSDE) in PRESS reduce editing efficiency. Single-voxel localization does not allow the characterization of spatial concentration differences. Therefore, our study introduces a robust MEGA-editing 3D-CSI sequence for 3T that uses LASER localization to eliminate CSDE; spiral encoding to accelerate acquisition; and real-time motion-/B0-correction with selective data reacquisition to eliminate subtraction artifacts.

Xiao-Hong Zhu¹, Byeong-Yeul Lee¹, Susan Rolandelli², Ming Lu¹, Paul Tuite², and Wei Chen^1
1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States, ²Department of Neurology, University of Minnesota Medical School, MN, United States

Energy failure from mitochondrial dysfunction has been proposed as a central mechanism leading to neuronal death in a range of neurodegenerative diseases. However, it is difficult to evaluate the link between abnormal energetics and impaired mitochondrial functions associated with neurodegeneration in living human brain. Recently a new high-field in vivo ³¹P MRS approach has been developed and its capability for non-invasively assessing the intracellular nicotinamide adenine dinucleotide (NAD) contents and its redox ratio has been demonstrated in healthy human brain at 7T. In the present study, we applied this newly developed method for quantitative assessment and comparison of NAD redox state in Parkinson’s disease (PD) patients and matched controls. The preliminary findings demonstrated abnormal cerebral energy metabolism associated with PD and the potential influences of gender in the disease.

Neil E. Wilson¹, Zohaib Iqbal¹, Brian L. Burns¹, Margaret A. Keller¹, and M. Albert Thomas^1
1University of California, Los Angeles, CA, United States

Perinatally HIV-infected youths often have compromised neurocognitive function that may be correlated with abnormal cerebral metabolite concentrations. Here, we look at 2D J-resolved spectra in a 3D acquisition acquired using an 8x undersampling and look for regional differences in metabolite concentrations between healthy and HIV-infected children. Two different reconstruction methods are compared.

Jun Chen¹, Jinhuan Liu¹, Zihu Tan², Qiong Yang², Hanchao Lan², Yilin Zhao¹, Dongjie Huang¹, Qizhong Xu¹, and Liang Zhang^1
1Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China, ²Department of Geriatrics, Hubei Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province, China

Vascular Cognitive Impairment No Dementia (VCIND) is introduced to identify the earliest stage of cognitive decline associated with vascular disease, which does not meet dementia criteria but with an increased risk of death and institutionalization1. Early detection of VCIND has significant clinical implications for a valid prognosis and treatement2. Proton magnetic resonance spectroscopy (1H-MRS) has been proved useful in investigating neurodegenerative diseases3. In this study, the therapeutic effect of Dioscorea modified pill and Aricept to VCIND patients was evaluated using brain 1H-MRS, mini-mental state examination (MMSE), clinical dementia rating (CDR) and Montreal Cognitive Assessment (MoCA) simultaneously and the relationship of these measurements was investigated as well.

Linda Chang¹, Caroline S. Jiang¹, Eric Cunningham¹, Steven Buchthal¹, Vanessa Douet¹, Marilou Andres², and Thomas Ernst^1
1Department of Medicine, University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, Hawaii, United States, ²University of Hawaii at Manoa, Pacific Biosciences Research Center, Honolulu, Hawaii, United States

Despite effective antiretroviral medications, milder forms of HIV-associated neurocognitive disorders (HAND) remain prevalent. The apolipoprotein-E(APOE)-4 gene was inconsistently found to increase the risk for HAND. Whether HIV subjects with APOE)-4 allele(s) would show greater neuroinflammation, which may contribute to cognitive deficits, is unknown and was evaluated. 177 participants (97 seronegative controls and 80 HIV subjects) were evaluated with ¹H MRS, cognitive assessments and genotyping for APOE. HIV subjects showed elevated levels of myoinositol regardless of APOE-4 genotype and across the agespan, which was associated with poorer cognitive function. APOE-4 combined with ¹H MRS may be useful markers to predict HAND.

Ralf Mekle¹, Simone Kuehn², Harald Pfeiffer¹, Florian Schubert¹, and Bernd Ittermann^1
1Medical Physics, Physikalisch-Technische Bundesanstalt, Berlin, Germany, ²Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany

The goal of this study was to detect differences in steady-state metabolite levels in response to a varying stimulation paradigm in the right human visual cortex using short TE ¹H MRS methodology at 7T. Instead of a strict on/off paradigm, where global physiologic effects might adversely influence MRS data acquisition, a modified stimulation condition not affecting the target voxel was employed as baseline. Nineteen metabolites were reliably quantified. A reduction of the neurotransmitter GABA and an increase of lactate were observed as the only significant effects. Differences with previous studies were attributed to the modified experimental conditions.

Marianne Cleve¹, Alexander Gussew¹, and Jürgen R. Reichenbach^1
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology I, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany

: This study comprises results of time resolved measurements of acute heat pain induced changes in excitatory (Glx) and inhibitory (GABA+) neurotransmitter turnover in the aCC by using 1H-MEGA-PRESS spectroscopy. Compared to the reference condition Glx/tCr increased significantly up to a median value of 14.2% in aCC during stimulation. At the same time, GABA+/tCr decreased by a median value of 25.4%. The Glx/tCr increase may be ascribed to the elevated glutamatergic turnover, while the GABA+/tCr decrease may reflect reduced activity of the inhibitory system during pain processing.